Brain, behavior, & immunity - health · 2025
Viral infections and risk of mental illness: A Mendelian randomization study.
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Huang Jian-Wei, Wang Yi-Fei, Tang Miao, Cui Qian-Qian, Guo Ying, Gao Shuang-Qi
Аннотация
BACKGROUND: Prior epidemiological evidence suggests associations between viral infections and psychiatric disorders, yet causal relationships remain insufficiently characterized. This study aims to investigate potential causal links using genetic instrumental variables.
METHODS: A two-sample Mendelian randomization (MR) analysis was conducted using pooled European-ancestry genomic data. Exposures included hepatitis B virus (HBV), human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human papillomavirus (HPV), and Epstein-Barr virus (EBV) infections. Outcomes encompassed generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), schizophrenia (SCH), major depressive disorder (MDD), and manic episodes. Causal estimates were primarily derived via inverse variance weighting (IVW), with robustness assessed through MR-Egger regression, weighted median, and pleiotropy-robust methods. Heterogeneity and horizontal pleiotropy were evaluated via Cochran's Qstatistic, MR-Egger intercept, and sensitivity plots.
RESULTS: HBV infection was associated with reduced GAD risk (OR = 0.94; 95 % CI [0.91, 0.97]; P = 0.0012). Similarly, HIV and SARS-CoV-2 infections exhibited protective effects against OCD (OR = 0.84; 95 % CI [0.72, 0.97]; P = 0.019 and OR = 0.78; 95 % CI [0.61, 0.99]; P = 0.039). HPV infection decreased SCH risk (OR = 0.84; 95 % CI [0.76, 0.92]; P = 0.0005). Conversely, EBV infection elevated MDD risk (OR = 1.00; 95 % CI [1.00, 1.01]; P = 0.0015). Sensitivity analyses confirmed minimal pleiotropy (Q > 0.05; MR-Egger intercept P > 0.1).
CONCLUSIONS: This MR analysis provides genetic evidence supporting causal roles of specific viral infections in psychiatric disorders. Findings underscore the clinical relevance of viral prevention strategies for mental health outcomes.
METHODS: A two-sample Mendelian randomization (MR) analysis was conducted using pooled European-ancestry genomic data. Exposures included hepatitis B virus (HBV), human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human papillomavirus (HPV), and Epstein-Barr virus (EBV) infections. Outcomes encompassed generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), schizophrenia (SCH), major depressive disorder (MDD), and manic episodes. Causal estimates were primarily derived via inverse variance weighting (IVW), with robustness assessed through MR-Egger regression, weighted median, and pleiotropy-robust methods. Heterogeneity and horizontal pleiotropy were evaluated via Cochran's Qstatistic, MR-Egger intercept, and sensitivity plots.
RESULTS: HBV infection was associated with reduced GAD risk (OR = 0.94; 95 % CI [0.91, 0.97]; P = 0.0012). Similarly, HIV and SARS-CoV-2 infections exhibited protective effects against OCD (OR = 0.84; 95 % CI [0.72, 0.97]; P = 0.019 and OR = 0.78; 95 % CI [0.61, 0.99]; P = 0.039). HPV infection decreased SCH risk (OR = 0.84; 95 % CI [0.76, 0.92]; P = 0.0005). Conversely, EBV infection elevated MDD risk (OR = 1.00; 95 % CI [1.00, 1.01]; P = 0.0015). Sensitivity analyses confirmed minimal pleiotropy (Q > 0.05; MR-Egger intercept P > 0.1).
CONCLUSIONS: This MR analysis provides genetic evidence supporting causal roles of specific viral infections in psychiatric disorders. Findings underscore the clinical relevance of viral prevention strategies for mental health outcomes.